NPASS Compound

Structure

NPC158285 OpenBabel06302216022D 35 40 0 0 1 0 0 0 0 0999 V2000 6.7089 2.3676 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4136 3.2765 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0530 3.9867 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9878 3.7880 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7578 4.8956 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3972 5.6057 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8230 5.0943 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1835 4.3841 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 5.4788 3.4752 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3140 4.7815 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5127 5.7163 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3140 3.8259 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.1413 3.3475 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1413 2.3915 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4855 2.3915 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6570 1.9132 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6570 0.9566 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8285 0.4783 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0000 0.9566 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8279 0.4784 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6558 0.9567 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6558 1.9133 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8279 2.3916 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8279 3.3677 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.9133 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0000 2.8894 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8285 2.3916 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8285 3.3476 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6570 3.8259 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4855 3.3476 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4855 4.3237 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4855 1.4154 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1594 4.3139 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6039 5.4210 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 9 1 0 0 0 0 2 3 2 0 0 0 0 3 4 1 0 0 0 0 3 5 1 0 0 0 0 5 6 2 0 0 0 0 5 7 1 0 0 0 0 7 8 1 0 0 0 0 8 9 1 0 0 0 0 8 10 1 6 0 0 0 10 11 1 6 0 0 0 10 12 1 0 0 0 0 10 35 1 0 0 0 0 12 30 1 0 0 0 0 12 13 1 0 0 0 0 12 34 1 1 0 0 0 13 14 1 0 0 0 0 14 15 1 0 0 0 0 15 30 1 0 0 0 0 15 16 1 0 0 0 0 15 33 1 6 0 0 0 16 17 1 6 0 0 0 16 27 1 0 0 0 0 18 17 1 1 0 0 0 18 19 1 0 0 0 0 18 32 1 0 0 0 0 19 25 1 0 0 0 0 19 20 1 6 0 0 0 19 32 1 0 0 0 0 20 21 1 0 0 0 0 21 22 2 0 0 0 0 22 23 1 0 0 0 0 23 24 2 0 0 0 0 23 25 1 0 0 0 0 25 26 1 1 0 0 0 25 27 1 0 0 0 0 27 28 1 1 0 0 0 28 29 1 0 0 0 0 29 30 1 0 0 0 0 30 31 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	422.21
Volume:	452.806
LogP:	6.1
LogD:	4.229
LogS:	-4.194
# Rotatable Bonds:	7
TPSA:	75.99
# H-Bond Aceptor:	5
# H-Bond Donor:	2
# Rings:	3
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.543
Synthetic Accessibility Score:	3.761
Fsp3:	0.346
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.645
MDCK Permeability:	1.4625077710661571e-05
Pgp-inhibitor:	0.386
Pgp-substrate:	0.017
Human Intestinal Absorption (HIA):	0.007
20% Bioavailability (F20%):	0.046
30% Bioavailability (F30%):	0.016

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.027
Plasma Protein Binding (PPB):	97.25144958496094%
Volume Distribution (VD):	0.822
Pgp-substrate:	1.7425096035003662%

ADMET: Metabolism

CYP1A2-inhibitor:	0.35
CYP1A2-substrate:	0.935
CYP2C19-inhibitor:	0.947
CYP2C19-substrate:	0.489
CYP2C9-inhibitor:	0.924
CYP2C9-substrate:	0.964
CYP2D6-inhibitor:	0.904
CYP2D6-substrate:	0.874
CYP3A4-inhibitor:	0.726
CYP3A4-substrate:	0.296

ADMET: Excretion

Clearance (CL):	15.399
Half-life (T1/2):	0.082

ADMET: Toxicity

hERG Blockers:	0.061
Human Hepatotoxicity (H-HT):	0.881
Drug-inuced Liver Injury (DILI):	0.667
AMES Toxicity:	0.016
Rat Oral Acute Toxicity:	0.741
Maximum Recommended Daily Dose:	0.774
Skin Sensitization:	0.511
Carcinogencity:	0.32
Eye Corrosion:	0.003
Eye Irritation:	0.581
Respiratory Toxicity:	0.94

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC158285

Natural Product ID:	NPC158285
*Common Name:**	RUVPNJSJTWTANE-LFCBYZEKSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	RUVPNJSJTWTANE-LFCBYZEKSA-N
Standard InCHI:	InChI=1S/C28H38O7/c1-15-13-20(34-22(30)16(15)2)25(5,31)28(33)12-11-26(32)18-14-21-27(35-21)9-6-7-19(29)24(27,4)17(18)8-10-23(26,28)3/h6-7,17-18,20-21,31-33H,8-14H2,1-5H3/t17-,18+,20+,21+,23-,24-,25-,26+,27+,28-/m0/s1
SMILES:	CC1=C(C)C(=O)O[C@H](C1)[C@@](C)([C@@]1(CC[C@]2([C@@H]3C[C@@H]4[C@@]5(CC=CC(=O)[C@]5(C)[C@H]3CC[C@]12C)O4)O)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	301751
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001560] Withanolides and derivatives

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO28734	Physalis peruviana	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28617598]
NPO28734	Physalis peruviana	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30649869]
NPO28734	Physalis peruviana	Species	Solanaceae	Eukaryota	Whole Fruits	n.a.	n.a.	PMID[32159343]
NPO28734	Physalis peruviana	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28734	Physalis peruviana	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
GI50	5
IC50	9
Others	2

Activity Type	# Activity
Cell Line	11
Individual Protein	2
NON-MOLECULAR	1
Others	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT134	Cell Line	SK-BR-3	Homo sapiens	GI50	=	710.0	nM	PMID[20438092]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	GI50	=	240.0	nM	PMID[20438092]
NPT83	Cell Line	MCF7	Homo sapiens	GI50	=	310.0	nM	PMID[20438092]
NPT396	Cell Line	T47D	Homo sapiens	GI50	=	160.0	nM	PMID[20438092]
NPT2601	Individual Protein	NF-kappaB inhibitor alpha	Homo sapiens	Inhibition	=	46.8	%	PMID[24900739]
NPT2601	Individual Protein	NF-kappaB inhibitor alpha	Homo sapiens	IC50	=	18000.0	nM	PMID[24900739]
NPT369	Cell Line	ACHN	Homo sapiens	IC50	=	489.0	nM	PMID[28257574]
NPT858	Cell Line	LNCaP	Homo sapiens	IC50	=	60.0	nM	PMID[28617598]
NPT1629	Cell Line	CWR22R	Homo sapiens	IC50	=	70.0	nM	PMID[28617598]
NPT369	Cell Line	ACHN	Homo sapiens	IC50	=	460.0	nM	PMID[28617598]
NPT387	Cell Line	M14	Homo sapiens	IC50	>	2000.0	nM	PMID[28617598]
NPT170	Cell Line	SK-MEL-28	Homo sapiens	IC50	>	2000.0	nM	PMID[28617598]
NPT859	Cell Line	HFF	Homo sapiens	IC50	>	2000.0	nM	PMID[28617598]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI50	=	420.0	nM	PMID[20438092]
NPT2	Others	Unspecified		Ratio IC50	=	10.0	n.a.	PMID[24900739]
NPT2	Others	Unspecified		IC50	=	980.0	nM	PMID[24900739]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC158285 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	263
0.1-0.2	1455
0.2-0.3	4197
0.3-0.4	7311
0.4-0.5	12473
0.5-0.6	7225
0.6-0.7	6533
0.7-0.8	2862
0.8-0.85	227
0.85-0.9	95
0.9-0.95	38
0.95-1	18

Similarity Score	Similarity Level	Natural Product ID

Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC158285 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	234
0.1-0.2	1600
0.2-0.3	3664
0.3-0.4	2354
0.4-0.5	742
0.5-0.6	286
0.6-0.7	156
0.7-0.8	109
0.8-0.85	4
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage

Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data